Evidence for the stress-linked immunocompetence handicap hypothesis in humans

Secondary sexual traits that develop under the action of testosterone, such as masculine human male facial characteristics, have been proposed to signal the strength of the immune system due to the sex hormone's immunosuppressive action. Recent work has suggested that glucocorticoid stress hormones may also influence expression of such sexual signals due to their effects on immune function. Precise roles, however, remain unclear. Here we show positive relationships between testosterone, facial attractiveness and immune function (antibody response to a hepatitis B vaccine) in human males, and present some preliminary evidence that these relationships are moderated by naturally co-occurring cortisol (a glucocorticoid stress hormone involved in the fight-or-flight response). We conclude that our results provide support for a role of glucocorticoids in hormonally mediated sexual selection

Lymphapheresis in organ transplantation: preliminary report.

Reduction of lymphoid tissue by splenectomy and/or thymectomy has been used as a part of immunosuppression in organ transplantation (4). More recently Walker (7), Johnson (2), Franksson (1) and Starzl (5,6) and their associates have shown that chronic depletion of lymphocytes by thoracic duct drainage decreases the incidence of rejection and hence increases renal graft survival. Mechanical removal of lymphocytes from circulation peripheral blood should theoretically achieve the same or similar effect on the immunity as thoracic duct drainage. Since September, 1979, five organ transplant recipients have received multiple lymphocytapheresis by IBM 2997 Blood Cell Separator as a mechanical pretransplant immunosuppression. The changes in cellular and humoral immunity and the clinical outcome are presented in this report

The Joker effect: cooperation driven by destructive agents

Understanding the emergence of cooperation is a central issue in evolutionary game theory. The hardest setup for the attainment of cooperation in a population of individuals is the Public Goods game in which cooperative agents generate a common good at their own expenses, while defectors "free-ride" this good. Eventually this causes the exhaustion of the good, a situation which is bad for everybody. Previous results have shown that introducing reputation, allowing for volunteer participation, punishing defectors, rewarding cooperators or structuring agents, can enhance cooperation. Here we present a model which shows how the introduction of rare, malicious agents -that we term jokers- performing just destructive actions on the other agents induce bursts of cooperation. The appearance of jokers promotes a rock-paper-scissors dynamics, where jokers outbeat defectors and cooperators outperform jokers, which are subsequently invaded by defectors. Thus, paradoxically, the existence of destructive agents acting indiscriminately promotes cooperation.Comment: Accepted for publication in the Journal of Theoretical Biology (JTB

Multi-scale interaction of flow and the artery wall

We discuss, from the perspective of basic science, the physical and biological processes which underlie atherosclerotic (plaque) initiation at the vascular endothelium, identifying their widely separated spatial and temporal scales which participate. We draw on current, related models of vessel wall evolution, paying particular attention to the role of flow, and proceed to propose, then validate (in practical, qualitative terms, at least) a multiply coupled, multi-scale modeling strategy, which, eventually, aims at a quantitative, patient-specific understanding of the coupling between the flow and the endothelial state

Efficiency of energy transfer, but not external work, is maximized in stunned myocardium

There is no evidence regarding the effect of stunning on maximization of regional myocardial external work (EW) or efficiency of energy transfer (EET) in relation to regional afterload (end-systolic stress, sigma(es)). To that end, we studied these relationships in both the left anterior descending coronary artery (LADCA) and left circumflex coronary artery regions in anesthetized, open-chest pigs before and after LADCA stunning. In normal myocardium, EET vs. sigma(es) was maximal at 75.4 (69.7-81.0)%, whereas EW vs. sigma(es) was submaximal at 12.0 (6.61-17.3) x 10(2) J/m(3). Increasing sigma(es) increased EW by 18 (10-27)%. Regional myocardial stunning decreased EET (27%) and EW (36%) and caused the myocardium to operate both at maximal EW (EW(max)) and at maximal EET (EET(max)). EET and EW became also more sensitive to changes in sigma(es). In the nonstunned region the situation remained unchanged. Combining the data from before and after stunning, both EW(max) and EET(max) displayed a positive relationship with contractility. In conclusion, the normal regional myocardium operated at maximal EET rather than at maximal EW. Therefore, additional EW could be recruited by increasing regional afterload. After myocardial stunning, the myocardium operated at both maximal EW and maximal EET, at the cost of increased afterload sensitivity. Contractility was a major determinant of this shift

Mechanical efficiency of stunned myocardium is modulated by increased afterload dependency

Oxygen consumption (MVO2) of stunned myocardium is relatively high compared to, and poorly correlated with, systolic contractile function. The aim of this study was to investigate whether an increased afterload dependency, induced by the decreased contractility of the stunned myocardium, contributes to the large variability in the mechanical efficiency data. Methods: In 13 anaesthetised open thorax pigs undergoing two cycles of 10 min occlusion of left anterior descending coronary artery and 30 min reperfusion, segment shortening, the slope of end systolic pressure segment length relationship (Ees), external work (EW, derived from the area inside the left ventricular pressure segment length loop), the efficiency of energy conversion (EET, = Embedded Image × 100%, where PLA = total pressure-segment length area), mechanical efficiency (Embedded Image), and their dependency on left ventricular end systolic pressure (Pes) were determined before and after induction of stunning, and during subsequent inotropic stimulation with dobutamine (1 and 3 μg·kg−1·min−1 over 15 min). Results: The stunning protocol not only caused significant decreases in segment shortening, external work, energy conversion efficiency, and Embedded Image but also increased the afterload dependency of these variab Before stunning an increase in Pes from 100 to 160 mm Hg decreased segment shortening from 18(SEM 1)% to 14(2)% (P > 0.05) and increased external work from 206(18) to 254(32) mm Hg·mm (P < 0.05). After induction of stunning the same increase in Pes caused a decrease in segment shortening from 9.5(1.8)% to −4.6(2.1)% (P < 0.05) and in external work from 149(21) to −11(10) mm Hg·mm (P < 0.05). The afterload dependency of the PLA was not altered by stunning, but the afterload dependency of energy conversion efficiency increased, since efficiency decreased from 67(3)% to 59(5)% as Pes was increased from 100 to 160 mm Hg before stunning, but from 57(5) to −7(5)% after induction of stunning (P < 0.05). Furthermore, the same increase in Pes resulted in an 8% decrease of Embedded Image before stunning and 107% after inducti stunning. Infusion of dobutamine not only restored segment shortening, external work, energy conversion efficiency, and Embedded Image of the stunned myocardium, but also attenuated their afterload dependency to levels. Conclusions: Myocardial stunning increases the afterload dependency of segment shortening, external work, energy conversion efficiency, and mechanical efficiency, which can be attenuated by inotropic stimulation with dobutamine. However, the decrease in left ventricular end systolic pressure, which accompanies the induction of stunning, counteracts the decrease in these variables. These two mechanisms can explain most of the reported scatter in mechanical efficiency

Heterogeneity of autoreactive T cell clones specific for the E2 component of the pyruvate dehydrogenase complex in primary biliary cirrhosis.

The extraordinary specificity of bile duct destruction in primary biliary cirrhosis (PBC) and the presence of T cell infiltrates in the portal tracts have suggested that biliary epithelial cells are the targets of an autoimmune response. The immunodominant antimitochondrial response in patients with PBC is directed against the E2 component of pyruvate dehydrogenase (PDC-E2). Hitherto, there have only been limited reports on the characterization and V beta usage of PDC-E2-specific cloned T cell lines. In this study, we examined peripheral blood mononuclear cells (PBMC) for their reactivity to the entire PDC complex as well as to the E1- and E2-specific components. We also examined the phenotype, lymphokine profile, and V beta usage of PDC-specific T cell clones isolated from cellular infiltrates from the livers of PBC patients. We report that PBMC from 16/19 patients with PBC, but not 12 control patients, respond to the PDC-E2 subunit. Interestingly, this response was directed to the inner and/or the outer lipoyl domains, despite the serologic observation that the autoantibody response is directed predominantly to the inner lipoyl domain. Additionally, lymphokine analysis of interleukin (IL) 2/IL-4/interferon gamma production from individual liver-derived autoantigen-specific T cell clones suggests that both T helper cell Th1- and Th2-like clones are present in the liver. Moreover, there was considerable heterogeneity in the T cell receptor for antigen (TCR) V beta usage of these antigen-specific autoreactive T cell clones. This is in contrast to murine studies in which animals are induced to develop autoimmunity by specific immunization and have an extremely limited T cell V beta repertoire. Thus, our data suggest that in human organ-specific autoimmune diseases, such as PBC, the TCR V beta repertoire is heterogenous